Lindegaard Marie L S, Nielsen Lars B
Department of Clinical Biochemistry, Rigshospitalet, 2100 Copenhagen, Denmark.
Metabolism. 2008 Jun;57(6):766-73. doi: 10.1016/j.metabol.2008.01.016.
Maternal diabetes is associated with increased transport of lipids to the fetus and increased risk of hypertrophic cardiomyopathy in the fetus. During fetal life, the heart normally has limited capacity to use lipids as fuel; and, at least in adults, cardiac lipid accumulation may lead to cardiomyopathy. Postnatally, lipid supply is increased when the offspring begins to suckle. We examined offspring from hypoinsulinemic Ins2(Akita) mice to assess whether maternal diabetes results in fetal myocardial hypertrophy and triglyceride accumulation and compared these with fetal hearts collected postnatally. On embryonic days 16 to 19, the fetal heart weight and triglyceride content were similar in offspring from Ins2(Akita) and nondiabetic wild-type mothers. The heart expression of lipid-metabolizing genes (peroxisomal proliferator-activated receptor alpha, lipoprotein lipase, fatty acid translocase, and fatty acid transport protein 1) was reduced in offspring from Ins2(Akita) mothers with high blood glucose levels and were closely intercorrelated, suggesting coordinated down-regulation. In contrast, on day 1 postnatally where the lipid availability to the heart is markedly increased, heart triglycerides and expression of several lipid-metabolizing genes (including lipoprotein lipase and fatty acid transport protein 1) were increased in offspring from wild-type mice. The results suggest that maternal type 1 diabetes mellitus in Ins2(Akita) mice does not cause cardiac hypertrophy or triglycerides accumulation in the fetal heart, possibly because of a coordinated down-regulation of genes controlling fatty acid uptake.
母体糖尿病与脂质向胎儿的转运增加以及胎儿肥厚型心肌病风险增加有关。在胎儿期，心脏通常利用脂质作为燃料的能力有限；并且，至少在成年人中，心脏脂质蓄积可能导致心肌病。出生后，当后代开始哺乳时脂质供应增加。我们检查了低胰岛素血症Ins2（Akita）小鼠的后代，以评估母体糖尿病是否会导致胎儿心肌肥厚和甘油三酯蓄积，并将其与出生后收集的胎儿心脏进行比较。在胚胎第16至19天，Ins2（Akita）和非糖尿病野生型母亲的后代的胎儿心脏重量和甘油三酯含量相似。脂质代谢基因（过氧化物酶体增殖物激活受体α、脂蛋白脂肪酶、脂肪酸转运蛋白和脂肪酸转运蛋白1）在血糖水平高的Ins2（Akita）母亲的后代心脏中的表达降低，且密切相关，提示协同下调。相比之下，在出生后第1天，心脏的脂质供应显著增加，野生型小鼠后代的心脏甘油三酯和几种脂质代谢基因（包括脂蛋白脂肪酶和脂肪酸转运蛋白1）的表达增加。结果表明，Ins2（Akita）小鼠的母体1型糖尿病不会导致胎儿心脏肥大或甘油三酯蓄积，这可能是由于控制脂肪酸摄取的基因协同下调所致。
